House dust mites are important as a major cause of allergic diseases such as atopic bronchial asthma.
Traditionally, hyposensitization therapy using a causative substance of allergy has been recognized as the most important basic approach to the treatment of allergic diseases, and its efficacy has already been well established in the treatment of allergic diseases caused by unavoidable inhaled allergen such as pollenosis, house dust allergy and fungal allergy.
However, this hyposensitization therapy necessitates administration of a safe therapeutic antigen since it involves a risk of anaphylaxis due to a sensitized antigen, and investigations are being made on such a sensitized antigen.
With respect to mite allergic diseases, two mite species, namely Dermatophagoides pteronyssinus and Dermatophagoides farinae are reported as important sources of allergen in house dust [Allerg. Asthma, 10, 329-334 (1964); J. Allergy, 42, 14-28 (1968)]. From these mite species, major mite allergens were fractionally separated and identified as glycoproteins (pI 4.6 to 7.2) having a molecular weight of 24 to 28 kD and/or proteins (pI 5 to 7.2) having a molecular weight of 14.5 to 20 kD, both of which are contained in mite excretion and/or mite bodies [J. Immunol., 125, 587-592 (1980); J. Allergy Clin. Immunol., 76, 753-761 (1985); Immunol., 46, 679-687 (1982); Int. Arch. Allergy Appl. Immunol., 81, 214-223 (1986); J. Allergy Clin. Immunol., 75, 686-692 (1985) and other publications].
However, none of the existing antigens for hyposensitization therapy is effective and safe.
Mite allergen genes have been cloned; for example, with respect to Der p I (molecular weight: 25,371) and Der p II (molecular weight: 14,131 and 17,460), the major allergens of Dermatophagoides pteronyssinus, and Der f II (the molecular weight remains undetermined because the initiation codon remains unidentified), the major allergen of Dermatophagoides farinae, the gene of each major allergen was cloned and its nucleotide sequences were determined [Int. Arch. Allergy Appl. Immunol., 85, 127-129 (1988); J. Exp. Med., 167, 175-182 (1988); J. Exp. Med., 170, 1457-1462 (1989); Int. Arch. Allergy Appl. Immunol., 91, 118-123 (1990); Int. Arch. Allergy Appl. Immunol., 91, 124-129 (1990); Jpn. J. Allergol., 39, 557-561 (1990); Agric. Biol. Chem., 55, 1233-1238 (1991)], and attempts have been made to study mite allergens by genetic recombination technology.
However, none of the existing mite allergens can serve as a sensitized antigen.
On the other hand, the diagnosis of mite allergic diseases has been mostly based on inquiry in combination with skin reaction test using a house dust extract and/or mite body extract, with measurements of serum IgE antibody titer (relative value) taken by the RAST (radio allergosorbent test) method, an inhalation provocation test and a nasal mucosal provocation test conducted concurrently in only a few cases. It has therefore been very difficult to make direct diagnosis of mite allergic diseases.
It has been the traditional practice to use a house dust extract for hyposensitization therapy for bronchial asthma caused by house dust mites as a specific antigen. However, it is subject to extreme limitation with respect to dose and its therapeutic effect is very low, since its chemical composition is very indefinite and it contains a wide variety of impure substances which may induce anaphylaxis.
Thus, from the viewpoint of efficacy and safety, it is desired to develop a useful antigen for hyposensitization therapy, and it is also expected that such a high quality antigen for hyposensitization therapy will be supplied stably.
However, it is difficult to stably supply such a safe mite allergen in sufficient amounts to ensure the desired effect by a method based on extraction and purification of mite allergen from mite culture because this method lacks mass-productivity and is subject to quantitative limitation.